Genetic Variant DMXL1:c.4970+21_4970+24dupAAAA (chr5-119165286-T-TAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000539542.6(DMXL1):c.4970+6_4970+7insAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

DMXL1
ENST00000539542.6 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.401

Publications

0 publications found

Variant links:

Genes affected

DMXL1 (HGNC:2937): (Dmx like 1) The protein encoded by this gene is a member of the WD repeat superfamily of proteins, which have regulatory functions. This gene is expressed in many tissue types including several types of eye tissue, and it has been associated with ocular phenotypes. In addition, it is upregulated in cultured cells that overexpress growth factor independence 1B, a transcription factor that is essential for hematopoietic cell development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

DMXL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000539542.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DMXL1	NM_001290321.3	MANE Select	c.4970+21_4970+24dupAAAA	intron	N/A	NP_001277250.1	F5H269
DMXL1	NM_001349239.2		c.4970+21_4970+24dupAAAA	intron	N/A	NP_001336168.1	F5H269
DMXL1	NM_001349240.2		c.4970+21_4970+24dupAAAA	intron	N/A	NP_001336169.1	Q9Y485

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DMXL1	ENST00000539542.6	TSL:1 MANE Select	c.4970+6_4970+7insAAAA	splice_region intron	N/A	ENSP00000439479.1	F5H269
DMXL1	ENST00000311085.8	TSL:1	c.4970+6_4970+7insAAAA	splice_region intron	N/A	ENSP00000309690.8	Q9Y485
DMXL1	ENST00000939842.1		c.4325+6_4325+7insAAAA	splice_region intron	N/A	ENSP00000609901.1

Frequencies

GnomAD3 genomes

AF:

0.0000525

AC:

AN:

114284

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000937

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000402

AC:

AN:

770310

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

398880

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

17838

American (AMR)

AF:

0.00

AC:

AN:

22268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16622

East Asian (EAS)

AF:

0.00

AC:

AN:

32276

South Asian (SAS)

AF:

0.0000417

AC:

AN:

47908

European-Finnish (FIN)

AF:

0.0000788

AC:

AN:

38060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2646

European-Non Finnish (NFE)

AF:

0.0000448

AC:

AN:

557904

Other (OTH)

AF:

0.0000287

AC:

AN:

34788

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.307

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000525

AC:

AN:

114284

Hom.:

Cov.:

AF XY:

0.0000183

AC XY:

AN XY:

54660

show subpopulations

African (AFR)

AF:

0.0000328

AC:

AN:

30460

American (AMR)

AF:

0.00

AC:

AN:

11428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2814

East Asian (EAS)

AF:

0.00

AC:

AN:

4542

South Asian (SAS)

AF:

0.00

AC:

AN:

3622

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0000937

AC:

AN:

53340

Other (OTH)

AF:

0.00

AC:

AN:

1598

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over